Racial differences in breast cancer (BrCa) incidence and mortality are unique among malignancies, in that risk of developing BrCa is higher in European-American women (EA) but risk of dying from it is higher in African-American women (AA). Why AAs suffer disproportionately high mortality rates may be explained in part by an excess of aggressive BrCa-hormone receptor negative and high-grade-in AAs, particularly the triple- negative breast cancer. Determining causes and consequences of racial/ethnic incidence differences is greatly facilitated by a clear understanding of the relevant descriptive epidemiology. To properly interpret the impacts of racial differences in BrCa characteristics on mortality rates, it is important to examine the incidence rates of clinically relevant subtypes, not just case proportions. Although age-specific and age-standardized incidence rates (metrics) of BrCa's defined by hormone receptor expression, histologic type OR stage are well established, such metrics for subtypes defined by combined estrogen receptor (ER) and histologic grade, known to be of both etiologic and prognostic importance, have not been well defined. We recently clarified AA vs EA BrCa incidence differences and similarities in South Carolina (SC) and Ohio, using these metrics plus relative incidence rate ratios (derived from Poisson regression modeling) for each of these subtypes. Differences between races were much greater than between the two states. Minimal inter-state differences in EA rates were found, but AAs had a 64% excess of ER negative high-grade cancer compared to EAs, in each state. In addition, AAs had a 25% higher incidence rate of ER positive lower-grade cancer in Ohio than in SC, consistent with Ohio having a more urban, racially admixed population. Age- standardization also reduced the racial difference in age at diagnosis typically observed by directly comparing cases by half or more, indicating the effect of population age structure on case age distributions. We hypothesize that similar patterns exist throughout the US. If true, discussion of racial disparities should focus on the profound and opposite disparities in incidence of prognostically important BrCa subtypes. We propose to determine how these metrics vary between races (AAs vs EAs) and geographic locations, and are impacted by inclusion of socioeconomic status (SES) indicators. We will use Surveillance, Epidemiology, and End Results (SEER) data from selected registries to determine the age-specific (5-year age groups) and age-standardized incidence rates for each ER/Grade subtype for the period 1996-2005. Poisson regression modeling methods will be used to compare AA and EA subtype rates, and to generate AA vs EA relative incidence rate ratios and other summary statistics. By focusing on ER/grade subtypes and going beyond case-case comparisons, this analysis will contribute meaningfully to discussion of etiologies of racial differences in BrCa incidence, and mortality, disparities and to predictions of future trends in these measures. (Italics indicate revisions from the original application.) PUBLIC HEALTH RELEVANCE: PUBLIC HEALTH SIGNIFICANCE Our recent analysis of age-specific and age-standardized breast cancer incidence rates in South Carolina and Ohio clarified profound and opposite racial disparities in biologically and clinically relevant breast cancer subtypes, with an ominous suggestion for future trends. Using SEER and Census tract data, we will test for similar findings in the various regions of the US, adjusting for socioeconomic indicators. We expect our work will contribute meaningfully to discussion of etiologies of racial differences in breast cancer incidence and mortality, and to predictions of future trends in the same, with important relevance for policy decisions aimed at reducing breast cancer health disparities and incidence overall.